New Medicines

Painful diabetic peripheral neuropathies (PDPN)


New molecular entity

Development and Regulatory status

Phase III Clinical Trials
Oct 19Helixmith announced plans to work on designing the next PIII trial to confirm data in the PIIIb extension study [5].
May 18Granted RMAT (Regenerative Medicine Advanced Therapy) designation in the US [6].


First-in-class non-viral plasmid DNA gene therapy which aims to restore blood flow to affected areas through regenerative angiogenesis. Aids formation of new microvasculature and re-myelination and regeneration of damaged nerves.[2,3]
In England, ~1 in 10 people aged 45-54 years have type 2 diabetes and about 1 in 4 people aged >75 years have it. Persistent painful neuropathy affects up to 1 in 4 people with type 2 diabetes. Over 50% of pts with type 2 diabetes aged >60 yrs have peripheral neuropathy. Around 1 in 300 people develop type 1 diabetes and type 1 diabetics usually develop neuropathy after >10 years of living with the condition. [1-3]
Painful diabetic peripheral neuropathies (PDPN)

Trial or other data

Nov 21PIII REGAiN-1A trial is recruiting [9].
May 21PIII REGAiN-1B 6-month extension trial to evaluate the durability of efficacy and long-term safety of IM administration of Engensis or placebo that was administered in the VMDN-003-2 trial starts (NCT04873232). Primary outcome is change from from the 7 days prior to the Day 0 Visit (Study VMDN-003-2) to 7 days prior to the Day 365 Visit in average daily pain score on the BPI-DPN; collection of these data is due to complete Mar 22 [9].
Oct 20PIII REGAiN-1A trial to evaluate the efficacy and safety of intramuscular (IM) administration of donaperminogene seltoplasmid on pain in patients with painful diabetic peripheral neuropathy (DPN) in the feet and lower legs, as compared to placebo starts (NCT04469270; VMDN-003-2). 152 adults will be recruited in the US. 16 injections of 0.25mg Engensis (0.5 mL) or 0.5mL placebo will be given in each of the right and left gastrocnemius muscles on Days 0, 14, 90, and 104. Primary outcome is average daily pain score from the Day 0 Visit to the Day 180 Visit on the Brief Pain Inventory for Participants with Diabetic Peripheral Neuropathy (scale 0-10) at 180 days; collection of primary outcome data due to complete Dec 22 [9].
Feb 20As previously reported, the initial PIII (DPN 3-1; NCT02427464; n=500, 9 months) did not meet its primary efficacy endpoint, but its double-blind placebo-controlled 3-month extension study (DPN 3-1B, a subset of N=101 subjects) met its primary endpoint (12 months long-term safety) and key secondary endpoint (analgesic efficacy at Day 365). Previously, Helixmith reported PK anomalies observed in the DPN 3-1 trial, indicating the possibility of mix-up of materials between placebo and active groups. The investigation has now been completed and root causes have been identified. The investigation revealed that there was no placebo-drug mix-up among the study subjects. Helixmith believes that VM202 has regeneration potential; the last follow-up visit of the extension study occurred more than 8 months from the last injection of VM2020. Understanding the difference in efficacy between DPN 3-1 and DPN 3-1B: Subjects in the DPN 3-1 and DPN 3-1B trials shared almost identical demographics and baseline characteristics, but there were clear differences in efficacy between the N=500 subjects enrolled in the full DPN 3-1 study and the subset of 101 subjects enrolled in the DPN 3-1B study. Results from additional post-hoc statistical analyses indicated that there was a noticeable difference between subjects enrolled in the first half and the second half of the trial. The company has identified possible causes, and the improvements will be implemented in the next Phase 3 trial. The company plans two or three independent PIII trials for painful DPN. One of these trials will be aimed to demonstrate the neuronal regenerative capacity of VM202 [8].
Dec 19No UK trial sites [7]
Oct 19Longer-term safety and efficacy of VM202 for painful DPN announced from PIIIb extension study. The extension study enrolled 101 pts (n=65 on VM202 group and n=36 on placebo) of the original 500 pts from the 3-month PIII DPN study. In this, VM202 showed clinically meaningful and statistically significant pain reductions vs. placebo at months 6, 9, and 12. The pain reduction differences between the arms at months 6, 9, and 12 were –1.1, –0.9, and –0.9, respectively (p-values were 0.010, 0.044, and 0.046). At 3 months, data showed a trend toward efficacy but the difference not statistically significant. The difference in pain reduction between the VM202 and placebo groups was greater in the population not on gabapentinoid medication. VM202 was safe and well-tolerated. [5]
Sep 19PIII study of VM202 vs. placebo in 500 pts with PDPN completed. The primary endpoint of 3 month pain change was not statistically meaningful athough it was well tolerated.[4]